Ovarian tumor is the fifth leading cause of cancer-related death and is difficult to diagnose and monitor. Although ovarian cancer accounts for about 4 percent of all cancers in women, it has the highest mortality of all gynecologic cancers, being a silent killer because it is often diagnosed at an advanced stage.
Ovarian cancer may be diagnosed, in part, by collecting a routine medical history from a patient and by performing physical examination, x-ray examination, and chemical and hematological studies on the patient. Hematological tests which may be indicative of ovarian cancer in a patient include analyses of serum levels of proteins designated CA125 and DF3 and plasma levels of lysophosphatidic acid (LPA). Palpation of the ovaries and ultrasound techniques (particularly including endovaginal ultrasound and color Doppler flow ultrasound techniques) can aid detection of ovarian tumors and differentiation of ovarian cancer from benign ovarian cysts. However, a definitive diagnosis of ovarian cancer typically requires performing exploratory laparotomy of the patient.
Thus, while abnormal growth corresponding to ovaries can be monitored by ultrasonography or by the serum marker, CA125, determining whether the growth is benign or malignant is not possible without biopsies. Biopsies are typically done after surgery and the tissue growth is taken for various pathological examinations. This is a tedious and time consuming procedure. The patient is usually out of the surgery room by the time the information is acquired.
Detection and proper measures for the control of the disease by surgery at the early stages can prevent the patient from undergoing agonizing radio and chemotherapy. Such procedures also often, in the most advanced cases, have no substantial curative effects.
Current diagnostic methods include serological diagnostics, which determine the level of CA-125, a protein produced by ovarian cancer cells. While CA-125 is an important test, it unfortunately is not always accurate. For example, some ovarian cancers may not produce enough CA-125 levels to cause a positive test result. Although the level of this antigen is elevated in nearly 80% of the patients with advanced stages of the cancer, expression may be low in early stages of ovarian cancer. Serum CA125 levels may also be falsely elevated in patients having other gynecological conditions like serosa of the peritoneum or pericardium, uterine fibroids, renal disorders or even pregnancy and normal menses.
Other current diagnostic methods include trans-vaginal ultrasound (TVU), which may be conducted alone or in combination with CA-125 testing. These methods can detect ovarian cancer but can also produce many false-positive test results. Use of ultrasound in conjunction with the CA125 has a positive predictive value of only 20%. It is estimated that three out of every four surgeries carried out are for non-malignant conditions, and these could possibly have been avoided saving the patients from the surgical trauma.
The diagnostic and prognostic tools presently available are therefore not adequate to predict the onset of the disease.
Genomic and proteomic techniques for the discovery of novel biomarkers for ovarian cancer from body fluids are known. The blueprints derived from these methods have recently shown assurance for early ovarian cancer detection, but further studies regarding their reproducibility and reliability for early detection and screening are needed.
Some of these proteins which are predicted to have a role as biomarker for ovarian cancer include M-CSF, mesothelin, α-folate receptor, OVX1, CA72-4, Prostasin, Osteopontin, Inhibin and Kallikrien.
Recently there has been an interest in using lysophosphatidic acid (LPA) as a biomarker for ovarian cancer. LPA has been shown to stimulate the proliferation of ovarian cancer cells and has been found in blood of ovarian cancer patients. LPA as a biomarker has been shown to have a sensitivity of 100% in advanced stage and almost 90% in the early stages.
However, the use of LPA as a biomarker for ovarian cancer has been highly controversial. In some studies no significant change in LPA levels in the ovarian cancer patients have been observed, raising questions about the utility of LPA as a biomarker. Some of the discrepancies were attributed to differences in the isolation protocol of plasma as activated platelets could also generate LPA. This lipid is also elevated in patients with other gynecological manifestations.
There is therefore a need for a method of detecting and diagnosing cancers such as ovarian cancers.